The versatile role of HuR in Glioblastoma and its potential as a therapeutic target for a multi-pronged attack.
The versatile role of HuR in Glioblastoma and its potential as a therapeutic target for a multi-pronged attack.
复制标题
DOI：
10.1016/j.addr.2021.114082
复制
发表时间：
2022-03
影响因子：
16.1
通讯作者：
King PH
中科院分区：
文献类型：
--
作者：
Guha A;Waris S;Nabors LB;Filippova N;Gorospe M;Kwan T;King PH
胶质母细胞瘤（GBM）是一种恶性和侵袭性脑肿瘤，中位生存期约为15个月。对治疗的抗性源于三种主要组分中广泛的细胞和分子异质性：神经胶质瘤肿瘤细胞、神经胶质瘤干细胞和肿瘤相关小胶质细胞和巨噬细胞。在这三个因素中，存在一个复杂的内在和分泌因子网络，这些因子促进癌症的经典特征，包括血管生成、抵抗细胞死亡、增殖和免疫逃避。连接这些不同途径的调控节点处于转录后水平，因为编码许多关键驱动因子的mRNA在3'非翻译区中含有腺嘌呤和尿苷富集元件（ARE）。人类抗原R（HuR）与ARE携带的mRNA结合，是该水平的主要正调控因子。本文综述了ARE介导的RNA调控的基本概念，以及如何用小分子抑制剂靶向HuR代表一种多管齐下的治疗GBM的可行策略。
Glioblastoma (GBM) is a malignant and aggressive brain tumor with a median survival of ~ 15 months. Resistance to treatment arises from the extensive cellular and molecular heterogeneity in the three major components: glioma tumor cells, glioma stem cells, and tumor-associated microglia and macrophages. Within this triad, there is a complex network of intrinsic and secreted factors that promote classic hallmarks of cancer, including angiogenesis, resisting cell death, proliferation, and immune evasion. A regulatory node connecting these diverse pathways is at the posttranscriptional level as mRNAs encoding many of the key drivers contain adenine- and uridine rich elements (ARE) in the 3’ untranslated region. Human antigen R (HuR) binds to ARE-bearing mRNAs and is a major positive regulator at this level. This review focuses on basic concepts of ARE-mediated RNA regulation and how targeting HuR with small molecule inhibitors represents a plausible strategy for a multi-pronged therapeutic attack on GBM.
登录
查看更多内容
影响因子：
14.9
作者：
Bakheet T;Williams BR;Khabar KS
通讯作者：
Khabar KS
DOI：
10.1016/j.bbagrm.2013.02.003
发表时间：
2013-06
影响因子：
4.7
作者：
Brooks, Seth A.;Blackshear, Perry J.
通讯作者：
Blackshear, Perry J.
影响因子：
7.3
作者：
Chen Z;Hambardzumyan D
通讯作者：
Hambardzumyan D
DOI：
10.1016/j.bbrc.2006.05.093
发表时间：
2006-07-21
影响因子：
3.1
作者：
Chen, Yu-Ling;Huang, Ya-Lin;Chang, Ching-Jin
通讯作者：
Chang, Ching-Jin
影响因子：
14.2
作者：
Casolaro, Vincenzo;Fang, Xi;Stellato, Cristiana
通讯作者：
Stellato, Cristiana